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Morphine-codeine interactions in rodents

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Field Value
Title Morphine-codeine interactions in rodents
Names Blank, Jerome W. (creator)
Larson, Robert E. (advisor)
Date Issued 1969-07-09 (iso8601)
Note Graduation date: 1970
Abstract Rats given morphine-codeine combinations exhibited significantly
increased hotplate reaction times compared with rats given
an analgesic dose of one agent alone. Genera, species, sex, protein
binding and metabolism were studied as possible implicating factors
for the increased reaction times. Both male and female rats exhibited
increased reaction time, and showed no difference in onset
and duration of the effect. When both analgesic and nonanalgesic
doses of one agent were given to rats concomitantly, the increased
reaction time was not produced. Thus the administration of both
drugs was necessary to produce the interaction. The increased
reaction time was not related to the method of measuring reaction
times, since the effect was demonstrated using both the tailflick
and hotplate techniques. A difference between genera was demonstrated
when the interaction could not be shown in mice.
Both morphine and codeine had one primary binding site in 3%
bovine serum albumin (BSA) solution. Morphine was bound in BSA
solution and rat plasma 49 ± 5% and 54 ± 4%, respectively. Codeine
was bound in BSA solution and rat plasma 59 ± 6% and 64 ± 5%,
respectively. The presence of one drug in varied amounts did not
significantly affect the binding characteristics of the other agent.
The dialyzable percent of the administered dose of morphine or
codeine was 24 ± 4% and 23 ± 5%, respectively. The presence of
one drug did not affect the dialyzable fraction of the other drug
when the two were administered to rats concomitantly.
Analysis of morphine metabolism in presence of varied concentrations
of codeine provided no evidence to support the idea that
codeine might be interfering with morphine metabolism. The presence
of varying amounts of morphine did not affect codeine metabolism.
Since no free morphine could be measured after codeine incubation,
there was no evidence to support the hypothesis that liberation
of morphine could be responsible for the increased reaction time.
The factors studied in this treatise did not determine a
mechanism for the interaction, but pointed out a possible genera
difference and defined the interaction more clearly.
Genre Thesis/Dissertation
Topic Morphine -- Physiological effect
Identifier http://hdl.handle.net/1957/46133

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